Microfluidic devices are becoming increasingly popular for performing analytical testing. Tools developed by the semiconductor industry for miniaturizing electronics enable fabrication and inexpensive mass production of intricate fluid systems. Microfluidic systems are increasingly utilized in performing a variety of analytical techniques for the acquisition of information in multiple disciplines, including the medical field, life sciences, and drug discovery and development.
There are different ways to manufacture microfluidic devices, including traditional lithographic techniques, soft lithography, and laminate technologies. In laminate fabrication the device consists of layers of material or lamina that have been cut, such as by a laser or stamp, into the desired shape and then held together with some form of adhesive, most commonly pressure-sensitive or thermally-activated adhesive. Maylar is commonly used, although other materials such as glass and polydimethylsiloxane (PMDS) have also been successfully incorporated into laminate devices. Microfluidic device construction may include a multi-layer laminated structure where each layer has channels and structures fabricated from a laminate material, forming microscale voids or channels where fluids flow. A microscale channel is generally defined as a fluid passage with at least one internal cross-sectional dimension that is less than 500 micrometers and typically between about 0.1 micrometers and about 500 micrometers. Either external pressurized fluid forced into the laminate or structures located within the laminate affect the control and pumping of fluids through these channels.
Under microfluidic conditions, fluids usually flow in a very predictable, laminar fashion, thereby allowing multiple fluids to flow next to each other in the same channel without turbulent mixing or the need for physical separation by a membrane. This is known as the laminar fluid diffusion interface. Smaller particles typically diffuse quickly across the boundary layer, whereas large molecules and particles, such as cells, typically diffuse only minimally.
U.S. Pat. No. 5,716,852 teaches a method for analyzing the presence and concentration of small particles in a flow cell using laminar flow and diffusion principles. Described is a channel cell system for detecting the presence of analyte particles in a sample stream using a laminar flow channel having at least two inlet means which provide an indicator stream and a sample stream, where the laminar flow channel has a depth sufficiently small to force laminar flow of the streams and length sufficient for diffusion of particles of the analyte into the indicator stream to form a detection area, and having an outlet out of the channel to form a single mixed stream. This device, which is known as a T-Sensor, may contain an external detecting means for detecting diffusion boundries in the indicator stream. This detecting means may be provided by any means known in the art, including optical means such as optical spectroscopy, or absorption spectroscopy of fluorescence.
Special challenges arise in employing devices that utilize the laminar fluid diffusion interface because preservation and maintenance of laminar flow in these devices relies heavily on precisely timed and controlled, as well as reproducible, introduction of several fluids into one channel. For example, fluids moved through multiple channels may converge and may pass through a single channel in a laminar fashion. However, precisely controlling both the timing and the change in volume of fluids entering the junction is generally necessary to prevent fluids from first reaching the outlet channel or obstructing a neighboring inlet channel before converging with other fluids, both of which may disturb laminar flow. Thus, a means of converging multiple fluids as to produce consistent laminar flow while allowing the appropriate control over the timing and the change in volume of converging fluids is desirable.